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The llamas have a much less appreciated feature: they form a whole body of immune system antibodies so small that they can penetrate the cracks on the surface of an invading virus.
This feat could one day protect humans from entire families of influenza viruses that hinder scientists with their unpredictable and ever-changing methods.
All potentially with a puff once a year.
In a study published Friday in the journal Science, a team at the Scripps Research Institute in La Jolla and their international colleagues have taken a major step toward achieving the long-sought goal of developing a universal flu vaccine.
When they tested their intranasal formulation in mice, it quickly gave full protection against a group of mouse-adapted human influenza strains. These include A viruses, such as the H1N1 "swine flu" virus that triggered a global pandemic in 2009, and B viruses, which only occur in humans.
Against H1N1, it has been shown that a dose of experimental vaccine protects for at least 35 days – a period equivalent to more than one influenza season in humans.
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, expressed deep appreciation for the new study, funded by the National Institutes of Health.
"From a scientific and technical point of view, it's really a very elegant study – the highest quality of science," Fauci said. He praised it for demonstrating that in order to protect people against pathogens that could change or emerge unpredictably, scientists had to design vaccines capable of destroying a large number of viruses, even at home. people whose immune system was fragile or compromised.
The flu is a viral plague that kills up to 650,000 people each year, according to the World Health Organization. To combat this phenomenon, the research team has borrowed new techniques from the laboratories of immunology, microbiology, nanotechnology and genetic engineering around the world.
First, they vaccinated llamas against a number of influenza A and B strains. They then took blood samples to collect the antibodies that the llamas produced in response.
Among them were four particularly small antibodies that demonstrated an ability to destroy many different strains of the flu. In a nod to their size and function, they called their creations "nanobodies".
From these small multitasking plants, researchers have developed a single protein that can sneak into spaces on the surface of the virus that are too small for most proteins. The resulting MD3606 multidomain antibody, with its "impressive width and power," could provide protection against just about every type of influenza nature could cause to mankind, the authors said. 'study.
If the dominant strain during a given season was to change suddenly, these antibodies would be ready for the unwelcome guest. If an influenza strain came from nowhere and threatened a population without immunity – the nightmare scenario of an influenza pandemic – this supercharged advocate would recognize this flu and counter it. If health officials were unaware of the future influenza strain and ordered a vaccine that would be largely ineffective – a scenario that was played out in the last influenza season – this set of antibodies could save the day.
However, researchers have encountered a major obstacle: to get the human immune system the ability to produce such a super-protein, even when weighed by age, stress and disease.
Their solution: do not even try.
Instead, they developed a way to circumvent the unreliable human response to vaccines, creating a gene that would code the production plans of their core protein. To transport this gene into a host organism, they have enlisted a harmless virus used by laboratories working on gene therapy.
By splicing their designer gene into this viral delivery device, scientists have not only found a way to get their antibody packets to a host, they have also provided the manufacturing equipment to help produce it. This "passive transfer" of antibodies gives this vaccine candidate the same potential for efficacy for everyone, said Fauci.
The next step is to do additional animal testing and human clinical trials, and it will take "years," he said. "But if all goes well – a majestic leap right now, it could eliminate the need for one season to another", guess which of the many possible influenza viruses would develop and then build an annual flu vaccine perfectly adapted to the situation.
The lead author of the study, Ian Wilson, an immunologist with Scripps, said that as cells "infected" with the transmission virus turn around, repeated doses may be needed to maintain antibody production. "We do not really know how long this treatment will survive in humans," he said.
But even less than permanent immunity against a wide range of influenza threats would help protect people from the appearance of unexpected influenza strains, Wilson said. And the rapid response of the mice to the vaccine suggests that it could be used to inoculate a population after the appearance of a new viral threat, he added.
The fact that the experimental vaccine has to be administered every year makes it an interesting hybrid, "said Ted M. Ross, director of the Center for Vaccines and Immunology at the University of Georgia.
"This approach is similar to the antivenom," Ross said. "Therapeutics is an antibody that has been made in another species to neutralize the toxin. This is short term, but it allows you to go through a period of time where bad things could happen. "
Over time, patients who repeatedly received the same antibodies could begin to develop resistance to them, he said. Vaccine manufacturers could remedy this by finding and including new antibodies in their formulation every few years, he suggested.
Ross and other scientists have also warned that the human immune system could see proteins derived from the llama as foreign proteins and attack them.
This is not the only universal influenza vaccine under development. In May, Fauci's NIAID launched the first clinical trial to test the safety of a universal influenza vaccine in 120 healthy people. The vaccine candidate, called M-001, targets parts of the influenza virus that tend to remain unchanged, as well as other proteins. This should encourage the human immune system to recognize and fight many different strains of influenza virus.
Janssen Vaccines and Prevention, a Dutch company that employs some of the authors of the study, has applied for a patent that would cover some of the molecules described in the new report.
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